BIOE 301 Lecture Eight

Review of Lecture 7 Science Engineering “Science is the human activity of seeking natural explanations for what we observe in the world around us.” Engineering Systematic design, production and operation of technical systems to meet practical human needs under specified constraints Six steps of the engineering design method

Q3: How can technology solve health care problems? CS1: Prevention of infectious disease

Roadmap of CS 1 Science Engineering Vaccines: From idea to product Organisms that cause disease Immunity Engineering How to make a vaccine Vaccines: From idea to product Societal Impact Health and economics Ethics of clinical trials Developed world/Developing world

Connections: First Day of Class Blood Plasma Cells Red blood cells White blood cells Platelets Cells made in bone marrow from pluripotent hematopoeitic stem cells

Neutrophil Lymphocyte Macrophage White Blood Cells Neutrophil Lymphocyte Macrophage

Pathogens How They Cause Disease

Types of Pathogens Bacteria Viruses Cells with membrane and cell wall (usually) Can survive outside host Can reproduce without a host Can be killed or inhibited by antibiotics Viruses Nucleic acid core with protein envelope Use host intracellular machinery to reproduce Cannot be killed with antibiotics >50 different viruses that can infect humans

Question: Based on your understanding of the characteristics of bacteria, viruses, and blood cells, identify which item best represents a bacterium, a virus and a blood cell and be able to explain why you chose each.

Bacteria

How do Bacteria Cause Disease? Invade host Reproduce Produce toxins which disturb function of normal cells

Virus

How do Viruses Cause Disease? Virus invades host cell Binds to cell membrane receptors Endocytosis brings virus into cell Virus takes over cell Use viral nucleic acid and host cell resources to make new viral nucleic acid and proteins More virus is released from host cell Virus causes host cell to lyse OR Viral particles bud from host cell surface

Pathophysiology of HIV/AIDS

Pathophysiology of HIV/AIDS

How Are We Protected Against Pathogens? The Immune System How Are We Protected Against Pathogens?

Types of Immunity Three layers of immunity: Keep pathogens out Physical Barriers Innate Immune System All animals possess Adaptive Immune System Vertebrates possess Keep pathogens out Kill them if they get in

Types of Immunity Physical Barriers Innate Immune System Skin (2 square meters) Mucous Membranes (400 square meters) Innate Immune System Produces general inflammatory response when pathogens penetrate physical barriers Adaptive Immune System Can adapt to defend against any invader Important when innate immune system cannot defend against attack Provides immune system with “memory”

Physical Barriers

What happens when you get a splinter?

What happens when you get a splinter? Pathogen makes it past a physical barrier Symptoms? Red, swollen, hot, pus What causes these symptoms? Innate immune system is kicking into gear Usually innate immune system can take care of it

What happens when you get a splinter? Macrophages eat bacteria on splinter Phagocytosis Produce chemicals which: Increase local blood flow Redness Heat Increase permeability of blood vessels Swelling Recruit other phagocytes to site of infection Pus

What happens when you get a splinter? Phagocytosis http://www.cellsalive.com/mac.htm WBCs in action http://cbr.med.harvard.edu/investigators/springer/lab/lab_goodies/lab_goodies.html

Innate Immune System Primarily effective against pathogens outside of cells Two main weapons: 1) Professional phagocytes Cells that eat stuff 2) The complement system Proteins that tag stuff for destruction

Components of Innate Immune System 1) Macrophages: Sentinels that patrol periphery If they find an invader, they become “activated” If activated, they: Send signals to recruit other immune system cells (Neutrophils) Become vicious killers Present antigen to adaptive immune system (more on this later)

Components of Innate Immune System 2) Complement proteins Present in tissues & blood Attach to surfaces of bacteria and viruses Target them for destruction by phagocytes Form Membrane Attack Complexes Recruit other immune cells from blood

Adaptive Immune System Two main components Fight pathogens outside of cells: 1) Antibodies Fight pathogens inside of cells: 2) Killer T cells

What is an antibody? Bridge between: Pathogen Tool to kill it Antibodies have two important regions: Fab region: Binds antigen Binds surface of virus infected cell Fc region: Binds macrophages and neutrophils, induces phagocytosis Binds natural killer cell, induces killing

Question: Which components of your kit are most like antibodies? Arrange the components of the kit to demonstrate how these antibodies “bridge” a pathogen and the tool to kill it?

Antibodies How are antibodies made? B cells Lymphocytes that make antibodies Have B cell receptors on surface 100 million different types of B cells, each with different surface receptors B cell receptors are so diverse they can recognize every organic molecule When a B cell binds antigen: Proliferates - In one week, clone of 20,000 identical B cells Secretes antibody

Adaptive Immune System How do we kill virus once inside the cell? Antibodies cannot get to it Need T cells T Cells Recognize protein antigens When bind antigen, undergo clonal selection Three types of T Cells: Killer T Cells (Cytotoxic T Lymphocytes – CTLs) Helper T Cells Regulatory T Cells

How do T Cells ID Virus Infected Cells? Antigen Presentation All cells have MHC molecules on surface When virus invades cell, fragments of viral protein are loaded onto MHC proteins T Cells inspect MHC proteins and use this as a signal to identify infected cells

Question: Using the components of the kit, demonstrate the two steps required for viral antigens to be presented on the MHC complexes on the surface of the blood cell.

Question: Demonstrate how the T cell can identify a virus infected cell. Why is this component of the adaptive immune system a significant advance over the innate immune system?

Immunologic Memory First time adaptive immune system is activated by an antigen: Build up a clone of B cells and T cells Takes about a week After infection is over, most die off Some remain – memory cells Second time adaptive immune system is activated by that antigen: Memory cells are easier to activate Response is much faster – no symptoms

Putting it all together

Summary of Lecture 8 Pathogens: Bacteria and Virus Levels of Immunity: Barriers  First line of defense Innate  Inflammation Phagocytes Complement Adaptive  Immunologic memory Antibody mediated immunity Cell mediated immunity  Pathogens within cells Diversity to recognize 100 million antigens

Next Time Two examples of viral infections: Vaccine Influenza HIV The most cost-effective medical intervention known to prevent death or disease Vaccine Video

Assignments Due Next Time HW6